New nanodrug design for cancer therapy: Its synthesis,formulation, in vitro and in silico evaluations

The aim of this study was to develop a novel nanosize drug candidate for cancer therapy. For this purpose, (S)-methyl 2-[(7-hydroxy-2-oxo-4-phenyl-2H-chromen-8-yl)methyleneamino]-3-(1H-indol-3-yl)propanoate (ND3) was synthesized by the condensation reaction of 8-formyl-7-hydroxy-4-phenylcoumarin with l -tryptophan methyl ester. Its controlled release formulation was prepared and characterized by different spectroscopic and imaging methods. The cytotoxic effects of ND3 and its controlled release formulation were evaluated against MCF-7 and A549 cancer cell lines, and it was found that both of them have a toxic effect on cancer cells. For drug design and process development, the molecular docking analysis technique helps to clarify the effects of some DNA-targeted anticancer drugs to determine the interaction mechanisms of these drugs on DNA in a shorter time and at a lower cost. By using the molecular docking analysis and DNA binding assays, the interaction between the synthesized compound and DNA was elucidated and non-binding interactions were also determined. To predict the pharmacokinetics, and thereby accelerate drug discovery, the absorption, distribution, metabolism, excretion and toxicity values of the synthesized compound were determined by in silico methods.     

Targeted mesenchymal stem cell and vascular endothelial growth factor strategies for repair of nerve defects with nerve tissue implanted autogenous vein graft conduits

Peripheral nerve gaps exceeding 1 cm require a bridging repair strategy. Clinical feasibility of autogenous nerve grafting is limited by donor site comorbidity. In this study we investigated neuroregenerative efficacy of autogenous vein grafts implanted with tissue fragments from distal nerve in combination with vascular endothelial growth factor (VEGF) or mesenchymal stem cells (MSCs) in repair of rat peripheral nerve defects. Six‐groups of Sprague‐Dawley rats (n = 8 each) were evaluated in the autogenous setting using a 1.6 cm long peroneal nerve defect: Empty vein graft (group 1), Nerve graft (group 2), Vein graft and nerve fragments (group 3), Vein graft and nerve fragments and blank microspheres (group 4), Vein graft and nerve fragments and VEGF microspheres (group 5), Vein graft and nerve fragments and MSCs (group 6). Nerve fragments were derived from distal segment. Walking track analysis, electrophysiology and nerve histomorphometry were performed for assessment. Peroneal function indices (PFI), electrophysiology (amplitude) and axon count results for group 2 were ?9.12 ± 3.07, 12.81 ± 2.46 mV, and 1697.88 ± 166.18, whereas the results for group 5 were ?9.35 ± 2.55, 12.68 ± 1.78, and 1566 ± 131.44, respectively. The assessment results did not reveal statistical difference between groups 2 and 5 (P > 0.05). The best outcomes were seen in group 2 and 5 followed by group 6. Compared to other groups, poorest outcomes were seen in group 1 (P ≤ 0.05). PFI, electrophysiology (amplitude) and axon count results for group 1 were ?208.82 ± 110.69, 0.86 ± 0.52, and 444.50 ± 274.03, respectively. Vein conduits implanted with distal nerve‐derived nerve fragments improved axonal regeneration. VEGF was superior to MSCs in facilitating nerve regeneration. © 2015 Wiley Periodicals, Inc. Microsurgery 36:578–585, 2016.     

Community-acquired hyperkalemia in elderly patients: risk factors and clinical outcomes

Background: Although the risk and related factors of hyperkalemia developed in the hospital are known in elderly, risk and related factors of community-acquired hyperkalemia (CAH) in this population are not well known. This study was performed to investigate the risk of CAH in elderly and evaluate the related factors and clinical outcomes.

Study design, setting and participants, intervention: Patients (aged ≥65 years) with hyperkalemia were screened. Group 1 (young-old); 65–74 years/old, Group 2 (middle-old); 75–84 years/old, Group 3 (oldest-old); ≥85 years/old, and Group 4 (control group); ≥65 years/old (normal serum potassium levels). The relation between CAH and hospital expenses (HE), the number of comorbid diseases (NCD), and all-cause of mortality rates (MR) were evaluated. We also investigated whether drugs, sex, and NCD are risk factors for the development of CAH.

Results: There was a positive correlation between serum potassium levels and length of hospital stay, MR, HE, and NCD (p?<?0.001). Risk factors for CAH were the use of non-steroidal-anti inflammatory drugs (NSAIDs) (Odds Ratio [OR]: 2.679), spironolactone (OR: 2.530), and angiotensin converting enzyme inhibitors (ACEI) (OR: 2.242), angiotensin receptor blockers (ARB) (OR: 2.679), ≥2 comorbid diseases (OR: 2.221), female gender (OR: 2.112), and renal injury (OR: 5.55). CAH risk was found to be increased 30.03 times when any of ACEI, ARB, NSAIDs, or spironolactone is given to a patient with a renal injury.

Conclusion: Use of NSAIDs, ACEI, ARB, spironolactone and increased NCD are all independent risk factors for CAH in the elderly, especially in patients with kidney diseases.     

Ultrasonographic evaluation of the femoral cartilage thickness in patients with chronic renal failure

Objective To investigate the effects of chronic renal failure (CRF) on the distal femoral cartilage thickness by using ultrasonography and to determine the relationship between cartilage thickness and certain disease-related parameters. Design Fifty-seven CRF patients (41 male and 16 female) (mean [SD] age, 44.7 [12.1] years) and 60 healthy controls (41 male and 19 female) (mean [SD] age, 43.5 [13.3] years) were enrolled in this study. Demographic and clinical characteristics were recorded. Cartilage thickness measurements were taken from the medial and lateral condyles, and intercondylar areas of both knees. Results Groups were similar in terms of age, weight, height, body mass index and gender (all p>0.05). The mean cartilage thickness was found to be less in CRF patients than in controls (statistically significant for medial condyles and intercondylar areas both in right and the left knees [all p<0.05]). Cartilage thickness showed no correlation with eGFR, and with the levels of serum urea, creatinine, calcium, magnesium, phosphor, hemoglobin, uric acid and as well as steroid use (all p>0.05) in CRF patients. Conclusion In the light of our findings, we imply that patients with CRF have thinner femoral cartilage than healthy controls. This result may support the view that patients with CRF are at increased risk for developing early knee osteoarthritis. Last but not least, clinicians should be aware of the importance of rehabilitation strategies aimed at decreasing onset and progression of knee osteoarthritis in patients with CRF.     

Perinatal trauma with and without loss experiences

Objective: The present study explored differences in mental health between women who experienced a trauma which involved a loss of fetal or infant life compared to women whose trauma did not involve a loss (difficult childbirth). Method: The sample consisted of 144 women (mean age = 31.13) from the UK, USA/Canada, Europe, Australia/New Zealand, who had experienced either stillbirth, neonatal loss, ectopic pregnancy, or traumatic birth with a living infant in the last 4 years. Results: The trauma without loss group reported significantly higher mental health problems than the trauma with loss group (F (1,117) = 4.807, p = .03). This difference was observed in the subtypes of OCD, panic, PTSD and GAD but not for major depression, agoraphobia and social phobia. However, once previous mental health diagnoses were taken into account, differences between trauma groups in terms of mental health scores disappeared, with the exception of PTSD symptoms. Trauma groups also differed in terms of perceived emotional support from significant others. Conclusion: The findings illustrate the need for a change in the focus of support for women’s birth experiences and highlighted previous mental health problems as a risk factor for mental health problems during the perinatal period.